RESUMO
INTRODUCTION: The mechanistic definition of chronic pancreatitis (CP) identifies acute pancreatitis (AP) as a precursor stage. We hypothesized that clinical AP frequently precedes the diagnosis of CP and is associated with patient- and disease-related factors. We describe the prevalence, temporal relationship and associations of AP in a well-defined North American cohort. METHODS: We evaluated data from 883 patients with CP prospectively enrolled in the North American Pancreatitis Studies across 27 US centers between 2000 and 2014. We determined how often patients had one or more episodes of AP and its occurrence in relationship to the diagnosis of CP. We used multivariable logistic regression to determine associations for prior AP. RESULTS: There were 624/883 (70.7%) patients with prior AP, among whom 161 (25.8%) had AP within 2 years, 115 (18.4%) within 3-5 years, and 348 (55.8%) >5 years prior to CP diagnosis. Among 504 AP patients with available information, 436 (86.5%) had >1 episode. On multivariable analyses, factors associated with increased odds of having prior AP were a younger age at CP diagnosis, white race, abdominal pain, pseudocyst(s) and pancreatic duct dilatation/stricture, while factors associated with a lower odds of having prior AP were exocrine insufficiency and pancreatic atrophy. When compared with patients with 1 episode, those with >1 AP episode were diagnosed with CP an average of 5 years earlier. CONCLUSIONS: Nearly three-quarters of patients were diagnosed with AP prior to CP diagnosis. Identifying which AP patients are at-risk for future progression to CP may provide opportunities for primary and secondary prevention.
Assuntos
Pancreatopatias , Pancreatite Crônica , Humanos , Doença Aguda , Pancreatite Crônica/complicações , Pancreatite Crônica/epidemiologia , Dor AbdominalRESUMO
INTRODUCTION: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects. METHODS: The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study. RESULTS: We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P < 4.885 × 10-23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2). DISCUSSION: A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.
Assuntos
Transtornos de Ansiedade/genética , Loci Gênicos/genética , Dor/etiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Idoso , Estudos de Coortes , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Dor/diagnóstico , População Branca/genéticaRESUMO
BACKGROUND & AIMS: Idiopathic chronic pancreatitis (ICP) is the second most common subtype of CP. In 1994, researchers reported the bimodal age at onset of ICP symptoms: early onset ICP (EO-ICP; median age, 19.2 y) and late-onset ICP (LO-ICP; median age, 56.2 y). Ages of onset and clinical features of ICP differed from those of alcohol-related CP (ACP). However, variants in PRSS1 had not yet been associated with ICP. We reexamined ages of onset of ICP in a large, North American cohort of patients, and investigated the effects of genetic factors and alcohol use in patients with EO-ICP, LO-ICP, and ACP. METHODS: We performed a cross-sectional analysis of patients with CP of European ancestry enrolled in the North American Pancreatitis Study 2, a prospective study of 1195 patients with CP from 26 centers in the United States from August 2000 through December 2014. We compared age at onset of symptoms for 130 patients with CP who were lifetime abstainers from alcohol (61 patients with early onset and 69 patients with late onset), 308 light to moderate alcohol drinkers with CP, and 225 patients with ACP and heavy to very heavy alcohol use. DNA from available patients was analyzed for variants associated with CP in SPINK1, CFTR, and CTRC. The Kruskal-Wallis test was used to compare continuous variables across groups and based on genetic variants. RESULTS: Median ages at onset of symptoms were 20 years for patients with EO-ICP and no alcohol use, 58 years for patients with LO-ICP and no alcohol use, 47 years for light to moderate alcohol drinkers with CP, and 44 years for patients with ACP. A higher proportion of patients with EO-ICP had constant pain (65%) than patients with LO-ICP (31%) (P = .04). A higher proportion of patients with ACP had pseudocysts (43%) than patients with EO-ICP (11%) (P = .001). A higher proportion of patients with EO-ICP had pathogenic variants in SPINK1, CFTR, or CTRC (49%) than patients with LO-ICP (23%), light to moderate alcohol drinking with CP (26%), or ACP (23%) (P = .001). Among patients with variants in SPINK1, those with EO-ICP had onset of symptoms at a median age of 12 years, and light to moderate alcohol drinkers with CP had an age at onset of 24 years. Among patients with variants in CFTR, light to moderate alcohol drinkers had an age at onset of symptoms of 41 years, but this variant did not affect age at onset of EO-ICP or ACP. CONCLUSIONS: We confirmed previously reported ages at onset of symptoms for EO-ICP and LO-ICP in a North American cohort. We found differences in clinical features among patients with EO-ICP, LO-ICP, and ACP. Almost half of patients with EO-ICP have genetic variants associated with CP, compared with approximately one quarter of patients with LO-CP or ACP. Genetic variants affect ages at onset of symptoms in some groups.
Assuntos
Pancreatite Crônica , Adulto , Idade de Início , Criança , Estudos Transversais , Humanos , Pessoa de Meia-Idade , América do Norte/epidemiologia , Pancreatite Crônica/complicações , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/genética , Estudos Prospectivos , Tripsina , Inibidor da Tripsina Pancreática de Kazal , Adulto JovemRESUMO
BACKGROUND: Pain is the most debilitating symptom of recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) and often requires chronic opioids or total pancreatectomy with islet autotransplantation to manage. Pain is a complex experience that can be exacerbated by depression and vice versa. Our aim was to test the hypothesis that depression-associated genes are associated with a constant-severe pain experience in RAP/CP patients. STUDY: A retrospective study was done using North American Pancreatitis Study II (NAPS2) genotyped RAP and CP patients with completed case report forms (n = 1,357). Subjects were divided based on pattern of pain and pain severity as constant-severe pain (n = 787) versus not constant-severe pain (n = 570) to conduct a nested genome-wide association study. The association between reported antidepressant medication use and depression gene loci was tested. RESULTS: Constant-severe pain was reported in 58% (n = 787) of pancreatitis patients. No differences in sex or alcohol consumption were found based on pain severity. Antidepressant use was reported in 28% (n = 223), and they had lower SF-12 mental quality of life (MCS, p < 2.2 × 10- 16). Fifteen loci associated with constant-severe pain (p < 0.00001) were found to be in or near depression-associated genes including ROBO2, CTNND2, SGCZ, CNTN5 and BAIAP2. Three of these genes respond to antidepressant use (SGCZ, ROBO2, and CTNND2). CONCLUSION: Depression is a major co-factor in the pain experience. This genetic predisposition to depression may have utility in counseling patients and in instituting early antidepressant therapy for pain management of pancreatitis patients. Prospective randomized trials are warranted. CLINICAL TRIALS REGISTRATION: Clinicaltriasl.gov.# NCT01545167.
Assuntos
Antidepressivos/administração & dosagem , Transtorno Depressivo Maior/epidemiologia , Dor/etiologia , Pancreatite Crônica/complicações , Adulto , Idoso , Estudos de Coortes , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/genética , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Dor/genética , Dor/psicologia , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
An amendment to this paper has been published and can be accessed via the original article.
RESUMO
INTRODUCTION: Diabetes mellitus (DM) is a complication of chronic pancreatitis (CP). Whether pancreatogenic diabetes associated with CP-DM represents a discrete pathophysiologic entity from type 2 DM (T2DM) remains uncertain. Addressing this question is needed for development of specific measures to manage CP-DM. We approached this question from a unique standpoint, hypothesizing that if CP-DM and T2DM are separate disorders, they should be genetically distinct. To test this hypothesis, we sought to determine whether a genetic risk score (GRS) based on validated single nucleotide polymorphisms for T2DM could distinguish between groups with CP-DM and T2DM. METHODS: We used 60 T2DM single nucleotide polymorphisms to construct a weighted GRS in 1,613 subjects from the North American Pancreatitis Study 2 and 2,685 subjects from the Multi-Ethnic Study of Atherosclerosis, all of European origin. RESULTS: The mean GRS was identical between 321 subjects with CP-DM and 423 subjects with T2DM (66.53 vs 66.42, P = 0.95), and the GRS of both diabetic groups was significantly higher than that of nondiabetic controls (n = 3,554, P < 0.0001). Exploratory analyses attempting to enrich the CP-DM group for pancreatogenic diabetes, such as eliminating diabetes diagnosed before CP, requiring pancreas-specific comorbidities, or removing those with a family history of diabetes, did not improve the ability of the GRS to distinguish between CP-DM and T2DM. DISCUSSION: Recognizing that we lacked a gold standard to define CP-DM, our study suggests that CP-DM may be a subtype of T2DM, a notion that should be tested in future, large prospective studies.
Assuntos
Diabetes Mellitus Tipo 2/genética , Pancreatite Crônica/complicações , Polimorfismo de Nucleotídeo Único/genética , Idoso , Estudos de Casos e Controles , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/epidemiologia , Fatores de RiscoRESUMO
OBJECTIVES: The aim of the present study was to investigate the natural history of chronic pancreatitis (CP); patients in the North American Pancreatitis Study2 (NAPS2, adults) and INternational Study group of Pediatric Pancreatitis: In search for a cuRE (INSPPIRE, pediatric) were compared. METHODS: Demographics, risk factors, disease duration, management and outcomes of 224 children and 1063 adults were compared using appropriate statistical tests for categorical and continuous variables. RESULTS: Alcohol was a risk in 53% of adults and 1% of children (Pâ<â0.0001); tobacco in 50% of adults and 7% of children (Pâ<â0.0001). Obstructive factors were more common in children (29% vs 19% in adults, Pâ=â0.001). Genetic risk factors were found more often in children. Exocrine pancreatic insufficiency was similar (children 26% vs adult 33%, Pâ=â0.107). Diabetes was more common in adults than children (36% vs 4% respectively, Pâ<â0.0001). Median emergency room visits, hospitalizations, and missed days of work/school were similar across the cohorts. As a secondary analysis, NAPS2 subjects with childhood onset (NAPS2-CO) were compared with INSPPIRE subjects. These 2 cohorts were more similar than the total INSPPIRE and NAPS2 cohorts, including for genetic risk factors. The only risk factor significantly more common in the NAPS2-CO cohort compared with the INSPPIRE cohort was alcohol (9% NAPS2-CO vs 1% INSPPIRE cohorts, Pâ=â0.011). CONCLUSIONS: Despite disparity in age of onset, children and adults with CP exhibit similarity in demographics, CP treatment, and pain. Differences between groups in radiographic findings and diabetes prevalence may be related to differences in risk factors associated with disease and length of time of CP.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Fumar Tabaco/efeitos adversos , Adolescente , Adulto , Criança , Estudos de Coortes , Estudos Transversais , Demografia , Progressão da Doença , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Pancreatite Crônica/genética , Pancreatite Crônica/fisiopatologia , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: We have previously reported that physicians under-recognize smoking as a chronic pancreatitis (CP) risk factor. We hypothesized that availability of empiric data will influence physician recognition of this relationship. METHODS: We analyzed data from 508 CP patients prospectively enrolled in the North American Pancreatitis Study-2 Continuation and Validation (NAPS2-CV) or NAPS2-Ancillary (AS) studies (2008-2014) from 26 US centers who self-reported ever-smoking. Information on smoking status, physician-defined etiology and identification of smoking as a CP risk factor was obtained from structured patient and physician questionnaires. We compared how often physician identified smoking as a CP risk factor in NAPS2-CV/NAPS2-AS studies with NAPS2-original study (2000-2006). RESULTS: Enrolling physician identified smoking as a risk factor in significantly (all pâ¯<â¯0.001) greater proportion of patients in NAPS2-CV/AS studies when compared with NAPS2-original study among ever (80.7 vs. 45.3%), current (91.3 vs. 53%), past (60.3 vs. 30.2%) smokers, in those who smoked ≤1 pack/day (79.3 vs. 39.5%) or ≥1 packs/day (83 vs. 49.8%). In multivariable analyses, the enrolling physician was 3.32-8.49 times more likely to cite smoking as a CP risk factor in the NAPS2-CV/NAPS2-AS studies based on smoking status and amount after controlling for age, sex, race and alcohol etiology. The effect was independent of enrolling site in a sub-analysis limited to sites participating in both phases of enrollment. CONCLUSIONS: Availability of empiric data likely enhanced physician recognition of the association between smoking and CP. Wide-spread dissemination of this information could potentially curtail smoking rates in subjects with and those at risk of CP.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Pancreatite Crônica/etiologia , Médicos , Fumar/efeitos adversos , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/tratamento farmacológico , Fatores de Risco , Autorrelato , Inquéritos e QuestionáriosRESUMO
BACKGROUND/OBJECTIVES: Our aim was to validate recent epidemiologic trends and describe the distribution of TIGAR-O risk factors in chronic pancreatitis (CP) patients. METHODS: The NAPS-2 Continuation and Validation (NAPS2-CV) study prospectively enrolled 521 CP patients from 13 US centers from 2008 to 2012. CP was defined by definitive changes in imaging, endoscopy, or histology. Data were analyzed after stratification by demographic factors, physician-defined etiology, participating center, and TIGAR-O risk factors. RESULTS: Demographics and physician-defined etiology in the NAPS2-CV study were similar to the original NAPS2 study. Mean age was 53 years (IQR 43, 62) with 55% males and 87% white. Overall, alcohol was the single most common etiology (46%) followed by idiopathic etiology (24%). Alcohol etiology was significantly more common in males, middle-aged (35-65 years), and non-whites. Females and elderly (≥65 years) were more likely to have idiopathic etiology, while younger patients (<35 years) to have genetic etiology. Variability in etiology was noted by participating centers (e.g., alcohol etiology ranged from 27 to 67% among centers enrolling ≥25 patients). Smoking was the most commonly identified (59%) risk factor followed by alcohol (53%), idiopathic (30%), obstructive (19%), and hyperlipidemia (13%). The presence of multiple TIGAR-O risk factors was common, with 1, 2, ≥3 risk factors observed in 27.6, 47.6, and 23.6% of the cohort, respectively. CONCLUSION: Our data validate the current epidemiologic trends in CP. Alcohol remains the most common physician-defined etiology, while smoking was the most commonly identified TIGAR-O risk factor. Identification of multiple risk factors suggests CP to be a complex disease.
Assuntos
Demografia/estatística & dados numéricos , Pancreatite Crônica/epidemiologia , Pancreatite Crônica/etiologia , Adulto , Fatores Etários , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Feminino , Humanos , Hiperlipidemias/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Grupos Raciais/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: Racial differences in susceptibility and progression of pancreatitis have been reported in epidemiologic studies using administrative or retrospective data. There has been little study, however, on the clinical profile, causes, and outcome of chronic pancreatitis (CP) in black patients. METHODS: We analyzed data on black patients with CP prospectively enrolled in the multicenter North American Pancreatitis Studies from 26 US centers during the years 2000-2014. CP was defined by definitive evidence on imaging studies or histology. Information on demographics, etiology, risk factors, disease phenotype, treatment, and perceived effectiveness was obtained from responses to detailed questionnaires completed by both patients and physicians. RESULTS: Of the 1,159 patients enrolled, 248 (21%) were black. When compared with whites, blacks were significantly more likely to be male (60.9 vs. 53%), ever (88.2 vs. 71.8%), or current smokers (64.2 vs. 45.9%), or have a physician-defined alcohol etiology (77 vs. 41.9%). There was no overall difference in the duration of CP although for alcoholic CP, blacks had a longer duration of disease (8.6 vs. 6.97 years; P=0.02). Blacks were also significantly more likely to have advanced changes on pancreatic morphology (calcifications (63.3 vs. 55.2%), atrophy (43.2 vs. 34.6%), pancreatic ductal stricture or dilatation (72.6 vs. 65.5%) or common bile duct stricture (18.6 vs. 8.2%)) and function (endocrine insufficiency 39.9 vs. 30.2%). Moreover, the prevalence of any (94.7 vs. 83%), constant (62.6 vs. 51%), and severe (78.4 vs. 65.8%) pain and disability (35.1 vs. 21.4%) were significantly higher in blacks. Observed differences were in part related to variances in etiology and duration of disease. No differences in medical or endoscopic treatments were seen between races although prior cholecystectomy (31.1 vs. 19%) was more common in white patients. CONCLUSIONS: Differences were observed between blacks and whites in the underlying cause, morphologic expression, and pain characteristics of CP, which in part are explained by the underlying risk factor(s) with alcohol and tobacco being much more frequent in black patients as well as disease duration.
Assuntos
Dor Abdominal/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Doenças do Ducto Colédoco/etnologia , Insuficiência Pancreática Exócrina/etnologia , Pancreatite Alcoólica/etnologia , Pancreatite Crônica/etnologia , Fumar/etnologia , População Branca/estatística & dados numéricos , Adulto , Idoso , Atrofia , Calcinose/etnologia , Constrição Patológica/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Pâncreas/patologia , Pancreatopatias/etnologia , Ductos Pancreáticos/patologia , Pancreatite Alcoólica/patologia , Pancreatite Crônica/etiologia , Pancreatite Crônica/patologia , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: Chronic pancreatitis is a significant medical problem that impacts a large number of patients worldwide. In 2014, we developed a disease-specific instrument for the evaluation of quality of life in this group of patients: pancreatitis quality of life instrument (PANQOLI). The goal of this study was to evaluate its psychometric properties: its reliability and its construct validity. METHODS: This is a cross-sectional multi-center study that involved 12 pancreatic disease centers. Patients who met the inclusion/exclusion criteria for chronic pancreatitis were invited to participate. Those who accepted were asked to complete seven questionnaires/instruments. Only patients who completed the PANQOLI were included in the study. Its reliability and its construct validity were tested. RESULTS: A total of 159 patients completed the PANQOLI and were included in the study. They had a mean age of 49.03, 49% were male, and 84% were Caucasian. Six of the 24 items on the scale were removed because of lack of inter-item correlation, redundancy, or lack of correlation to quality of life issues. The final 18-item scale had excellent reliability (Cronbach's alpha coefficient: 0.914) and excellent construct validity with good correlation to generic quality of life instruments (SF-12 and EORTC QLQ-C30/QLQ-PAN26) and lack of correlation to non-quality of life instruments (MAST and DAST). Through exploratory factor analysis, the PANQOLI was found to consist of four subscales: emotional function scale, role function scale, physical function scale, and "self-worth" scale. CONCLUSIONS: PANQOLI is the first disease-specific instrument to be developed and validated for the evaluation of quality of life in chronic pancreatitis patients. It has a unique subscale for "self-worth" that differentiates it from other generic instruments. Studies are currently under way to evaluate its use in other populations not included in this study.
Assuntos
Atividades Cotidianas , Pancreatite Crônica/psicologia , Qualidade de Vida/psicologia , Autoimagem , Adulto , Estudos Transversais , Análise Fatorial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/fisiopatologia , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: Since 1985, the American Society for Gastrointestinal Endoscopy (ASGE) has awarded grants for endoscopic-related research. The goals of this study were to examine trends in ASGE grant funding and to assess productivity of previous recipients of the ASGE grant awards. METHODS: This was a retrospective cohort analysis of all research grants awarded by the ASGE through 2009. Measures of academic productivity and self-assessment of the ASGE awards' impact on the recipients' careers were defined by using publicly available resources (eg, National Library of Medicine-PubMed) and administration of an electronic survey to award recipients. RESULTS: The ASGE awarded 304 grants totaling $12.5 million to 214 unique awardees. Funding increased 7.5-fold between 1985 and 1989 (mean $102,000/year) and between 2005 and 2009 (mean $771,000/year). The majority of awardees were men (83%), were at or below the level of assistant professor (82%), with a median of 3 years of postfellowship experience at the time of the award, and derived from a broad spectrum of institutions as measured by National Institutes of Health funding rank (median 26, interquartile range [IQR] 12-64). Nineteen percent had a master's degree in a research-related field. Awardees' median publications per year increased from 3.5 (IQR 1.2-9.0) before funding to 5.7 (IQR 1.8-9.5) since funding; P = .04, and median h-index scores increased from 3 (IQR 1-8) to 17 (IQR 8-26); P < .001. Multivariate analysis found that the presence of a second advanced degree (eg, masters or doctorate) was independently predictive of high productivity (odds ratio [OR] 2.92; 95% confidence interval [CI], 1.09-7.81). Among 212 unique grant recipients, 82 (40%) completed the online survey. Of the respondents, median peer-reviewed publications per year increased from 3.4 (IQR 1.9-5.5) to 4.5 (IQR 2.0-9.5); P = .17. Ninety-one percent reported that the ASGE grant had a positive or very positive impact on their careers, and 85% of respondents are currently practicing in an academic environment. Most of the grants resulted in at least 1 peer-reviewed publication (67% per Internet-based search and 81% per survey). CONCLUSIONS: The ASGE research program has grown considerably since 1985, with the majority of grants resulting in at least 1 grant-related publication. Overall academic productivity increased after the award, and the majority of awardees report a positive or very positive impact of the award on their careers. Medical professional societies are an important sponsor of clinical research.
Assuntos
Pesquisa Biomédica , Gastroenterologia , Apoio à Pesquisa como Assunto , Estudos de Coortes , Eficiência , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , National Institutes of Health (U.S.) , Editoração , Pesquisadores , Estudos Retrospectivos , Sociedades Médicas , Estados UnidosRESUMO
BACKGROUND AND AIMS: Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as an alternative to traditional radiologic and surgical drainage procedures after failed endoscopic retrograde cholangiopancreatography (ERCP). However, prospective multicenter data are lacking. The aims of this study were to prospectively assess the short- and long-term efficacy and safety of EUS-BD in patients with malignant distal biliary obstruction. PATIENTS AND METHODS: Consecutive patients at 12 tertiary centers (5 US, 5 European, 1 Asian, 1 South American) with malignant distal biliary obstruction and failed ERCP underwent EUS-BD. Technical success was defined as successful stent placement in the desired position. Clinical success was defined as a reduction in bilirubin by 50â% at 2 weeks or to below 3âmg/dL at 4 weeks. Adverse events were prospectively tracked and graded according to the American Society for Gastrointestinal Endoscopy (ASGE) lexicon's severity grading system. Overall survival and duration of stent patency were calculated using Kaplan-Meier analysis. RESULTS: A total of 96 patients (mean age 66 years, female 45â%, pancreatic cancer 55â%) underwent EUS-BD. Stent placement (technical success) was achieved in 92 (95.8â%) patients (metallic stent 84, plastic stent 8). Mean procedure time was 40 minutes. Clinical success was achieved in 86 (89.5â%) patients. A total of 10 (10.5â%) adverse events occurred: pneumoperitoneum (nâ=â2), sheared wire (nâ=â1), bleeding (nâ=â1), bile leak (nâ=â3), cholangitis (nâ=â2), and unintentional perforation (nâ=â1); 4 graded as mild, 4 moderate, 1 severe, and 1 fatal (due to perforation). A total of 38 (44â%) patients died of disease progression during the study period. The median patient survival was 167 days (95â%CI 112â-â221) days. The 6-month stent patency rate was 95â% (95â%CI 94.94â-â95.06â%) and the 1-year stent patency was 86â% (95â%CI 85.74â-â86.26â%). CONCLUSION: This study on EUS-BD demonstrates excellent efficacy and safety of EUS-BD when performed by experts. STUDY REGISTRATION: NCT01889953.
RESUMO
BACKGROUND: The combination of prophylactic pancreatic stent placement (PSP) - a temporary plastic stent placed in the pancreatic duct - and rectal non-steroidal anti-inflammatory drugs (NSAIDs) is recommended for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Preliminary data, however, suggest that PSP may be unnecessary if rectal NSAIDs are administered. Given the costs and potential risks of PSP, we aim to determine whether rectal indomethacin obviates the need for pancreatic stent placement in patients undergoing high-risk ERCP. METHODS/DESIGN: The SVI (Stent vs. Indomethacin) trial is a comparative effectiveness, multicenter, randomized, double-blind, non-inferiority study of rectal indomethacin alone versus the combination of rectal indomethacin and PSP for preventing PEP in high-risk cases. One thousand four hundred and thirty subjects undergoing high-risk ERCP, in whom PSP is planned solely for PEP prevention, will be randomized to indomethacin alone or combination therapy. Those who are aware of study group assignment, including the endoscopist, will not be involved in the post-procedure care of the patient for at least 48 hours. Subjects will be assessed for PEP and its severity by a panel of independent and blinded adjudicators. Indomethacin alone will be declared non-inferior to combination therapy if the two-sided 95 % upper confidence bound of the treatment difference is less than 5 % between the two groups. Biological specimens will be obtained from trial participants and centrally banked. DISCUSSION: The SVI trial is designed to determine whether PSP remains necessary in the era of NSAIDs pharmacoprevention. The associated bio-repository will establish the groundwork for important scientific breakthrough. TRIAL REGISTRATION: NCT02476279, registered June 2015.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Colangiopancreatografia Retrógrada Endoscópica/instrumentação , Indometacina/administração & dosagem , Pancreatite/prevenção & controle , Stents , Administração Retal , Anti-Inflamatórios não Esteroides/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Protocolos Clínicos , Terapia Combinada , Feminino , Humanos , Indometacina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/etiologia , Projetos de Pesquisa , Medição de Risco , Fatores de Risco , Fatores de Tempo , Bancos de Tecidos , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE: Historically, chronic pancreatitis (CP) was considered a disease of alcoholic males, but recent data suggest its etiology to be complex. To better understand CP in women, we compared data on women and men with CP in a large, prospectively ascertained multicenter US cohort. METHODS: Patients with CP enrolled in the NAPS2 Continuation and Validation study were studied. Information on demographics, etiology, risk factors, phenotype, and treatment(s) used was obtained from detailed questionnaires completed by the patients and physicians. RESULTS: Of 521 cases, 45% were women. Women were significantly (P < 0.05) less likely to have alcohol etiology (30% vs 58.5%) and more likely to have nonalcoholic etiologies (idiopathic, 32% vs 18%; obstructive, 12% vs 2.4%; genetic, 12.8% vs 7.3%). Demographics, pain experience, morphologic findings, exocrine and endocrine insufficiency, CP-related disability, and use of medical therapies were mostly similar in both sexes. Sphincterotomy (biliary, 33% vs 24%; pancreatic, 38% vs 28%; P < 0.05) was performed more frequently in women, whereas cyst/pseudocyst operations were more common in men (6.6 vs 2.6%, P = 0.02). CONCLUSIONS: Most CP cases in women are from nonalcoholic etiologies. In contrast to many other chronic diseases, clinical phenotype of CP is determined by the disease and is independent of sex.
Assuntos
Pancreatite Crônica/diagnóstico , Pancreatite Crônica/terapia , Inquéritos e Questionários , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite Crônica/etiologia , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Estados Unidos , Adulto JovemRESUMO
IMPORTANCE: Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. OBJECTIVE: To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. DESIGN, SETTING, AND PARTICIPANTS: Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. INTERVENTIONS: Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. MAIN OUTCOMES AND MEASURES: Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of -15%. RESULTS: There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, -3.0% to ∞; P < .001). Given the prespecified noninferiority margin of -15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). CONCLUSIONS AND RELEVANCE: Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01221311.
Assuntos
Colestase/terapia , Stents , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/estatística & dados numéricos , Colestase/etiologia , Constrição Patológica/etiologia , Constrição Patológica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Plásticos , Complicações Pós-Operatórias/terapia , Implantação de Prótese , Tamanho da Amostra , Stents Metálicos Autoexpansíveis/efeitos adversos , Stents/efeitos adversosRESUMO
BACKGROUND AND STUDY AIM: Pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP) is a significant and potentially life-threatening adverse event and is common in patients with suspected sphincter of Oddi dysfunction (SOD). Here we aimed to identify predictors of the risk in this population. PATIENTS AND METHODS: The Evaluating Predictors and Interventions in SOD (EPISOD) study prospectively enrolled 214 post-cholecystectomy patients with SOD type III in seven US centers. Patients were randomized, using a 2:1 allocation, to sphincterotomy or sham procedure, irrespective of the results of sphincter of Oddi manometry. Patients in the sphincterotomy arm who had elevated pancreatic sphincter pressure were randomized to biliary only or to dual (biliary and pancreatic) sphincterotomy. All but one patient received prophylactic pancreatic stents, but none received pharmacological prophylaxis. Post ERCP pancreatitis (PEP) was defined as acute pancreatitis within the subsequent 7 days. Blinded research coordinators at each site called patients at 1 week post-procedure. RESULTS: PEP occurred in 26 patients, in 10.6â% (15/141) in the sphincterotomy arm and 15.1â% (11/73) in the sham arm; unadjusted relative risk 0.71 (95â% confidence interval [95â%CI] 0.34â-â1.46). PEP rate was not significantly different in patients who received sphincterotomy compared with those undergoing sham treatment. In addition, the proportion was not statistically different in those who received biliary sphincterotomy alone (12/94; 12.8â% [95â%CI 6.0â%â-â19.5â%]) compared with dual sphincterotomy (3/47; 6.4â% [95â%CI 0.0â%â-â13.4â%]). Multivariate analysis identified an interaction between duration of ERCP and sedation type (Pâ<â0.02). CONCLUSION: The performance of biliary or dual sphincterotomy does not increase the risk of PEP in patients suspected of SOD. However, the high rate of PEP in patients with suspected SOD, despite pancreatic stenting in expert centers, is confirmed in this prospective study. The combined effect of duration of ERCP and sedation type on the development of PEP should be further explored.Clinicaltrials.gov registration: NCT00688662.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Doenças do Ducto Colédoco/cirurgia , Pancreatite/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Disfunção do Esfíncter da Ampola Hepatopancreática/cirurgia , Esfíncter da Ampola Hepatopancreática/fisiopatologia , Esfinterotomia Endoscópica/efeitos adversos , Adulto , Doenças do Ducto Colédoco/fisiopatologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Manometria , Pessoa de Meia-Idade , Pancreatite/diagnóstico , Pancreatite/etiologia , Complicações Pós-Operatórias/diagnóstico , Pressão , Prognóstico , Estudos Prospectivos , Esfíncter da Ampola Hepatopancreática/cirurgia , Disfunção do Esfíncter da Ampola Hepatopancreática/diagnóstico , Disfunção do Esfíncter da Ampola Hepatopancreática/fisiopatologia , Stents , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Sphincter of Oddi dysfunction (SOD) has long been a controversial topic, starting with whether it even exists, as a sphincterotomy-responsive entity to treat, for either: (1) post-cholecystectomy abdominal pain and/or (2) idiopathic recurrent acute pancreatitis (IRAP). Many of its aspects had required further research to better prove or refute its existence and to provide proper recommendations for physicians to diagnose and treat this condition. Fortunately, there has been major advancement in our knowledge in several areas over the past few years. New studies on challenging the classification, exploring alternative diagnostic methods, and quantifying the role of sphincterotomy in treatment of SOD for post-cholecystectomy pain and for IRAP were recently published, including a randomized trial in each of the two areas. The goal of this paper is to review recent literature on selected important questions and to summarize the results of major trials in this field.
Assuntos
Disfunção do Esfíncter da Ampola Hepatopancreática/diagnóstico , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Imageamento por Ressonância Magnética , Manometria/métodos , Pancreatite/etiologia , Índice de Gravidade de Doença , Esfíncter da Ampola Hepatopancreática/fisiopatologia , Esfíncter da Ampola Hepatopancreática/cirurgia , Disfunção do Esfíncter da Ampola Hepatopancreática/psicologia , Disfunção do Esfíncter da Ampola Hepatopancreática/terapia , Esfinterotomia Endoscópica , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND: Single-balloon enteroscopy (SBE) was introduced in 2007 to diagnose and treat small-bowel disorders. No study to date has evaluated SBE in patients with surgically altered anatomy outside of ERCP. OBJECTIVE: To evaluate the efficacy, yield, and safety of SBE in patients with surgically altered anatomy. DESIGN: Retrospective study. SETTING: Tertiary-care academic medical center. PATIENTS: All patients with altered surgical anatomy who underwent SBE at the Medical University of South Carolina from July 2007 to September 2013. INTERVENTIONS: SBE. MAIN OUTCOME MEASUREMENTS: Diagnostic yield, therapeutic yield, technical success, and adverse events. RESULTS: A total of 48 patients met inclusion criteria. Mean age was 56 years (77% female). Eleven patients underwent single-balloon PEG placement, 8 single-balloon ERCP, 22 non-PEG/non-ERCP anterograde SBE, and 7 retrograde SBE. Previous surgeries included Roux-en-Y gastric bypass (n=26), small-intestine resection (n=6), colon resection (n=5), Whipple procedure (n=4), choledochojejunostomy (n=3), hepaticojejunostomy (n=1), Billroth I (n=1), Billroth II (n=1), and Puestow procedure (n=1). Procedural indications were PEG tube placement (n=11), choledocholithiasis (n=2), biliary stricture (n=2), obstructive jaundice (n=1), cholangitis (n=1), ampullary mass (n=1), sphincter of Oddi dysfunction (n=1), anemia and/or bleeding (n=15), abdominal pain (n=9), radiologic evidence of obstruction (n=3), and Peutz-Jeghers syndrome (n=2). The technical success rate was 73% in single-balloon PEG placement, 88% in single-balloon ERCP, 82% in other anterograde SBEs, and 86% in retrograde SBEs. No intraprocedural or postprocedural adverse events were observed. LIMITATIONS: Single center, retrospective study. CONCLUSION: SBE is safe and effective in patients with surgically altered anatomy.